REVERSE AGING: What To Eat & When To Eat For LONGEVITY | David Sinclair

Adversity, right? What doesn't kill you makes you live longer.

Oh, that's a good one. So put your body through pain throughout your life as consistently as possible. Like controlled pain, right? Going in a sauna for 15 minutes and pushing an extra minute. Like that feeling of adversity, going in cold, working out hard, doing something where it's a. You're not gonna kill yourself or hurt or break a leg, but it's like. Alfred. Is that what I'm hearing?

That's the most important lesson.

Welcome back, everyone, in the School of Greatness podcast. We have the iconic Dr. David Sinclair in the house. Thank you so much for being here. Very excited about this. You are the master on talking about lifespan, talking about how to reverse aging, talking about how to extend our life, our health, and everything. And something you said before we got on here and that I read in your book is that aging is a disease, is that right?

Well, that's what I think, yeah.

That's what you think it is. Would that mean death is a disease as well?

Well, death is the end product of aging.

Okay.

So we've cured just about every other major disease. So you don't die from an infection. You typically don't die in childbirth if you're a woman. So now what's left is aging. And while we're whacking each of these diseases, cancer, heart disease, Alzheimer's, we're trying to whack them on the head like a whacK-A-Mole game. We forget that the main reason all these diseases occur is that our bodies are aging. If you don't get old, you don't get those diseases.

Is that because your immune system is strong and so that it fights against disease essentially?

Well, yes, it's similar, but it's not the immune system that you're thinking of. We actually have inbuilt defenses, we call them longevity genes, that we can activate in our daily lives by doing certain things.

Longevity genes.

Yes, that's what we call them.

How many genes do we have?

Oh, we've got about 23, 24,000 of them.

23 or 24,000 genes.

Right, but there's only about 50 really important ones for longevity.

Okay, and what are the ones of this longevity gene?

Well, the ones we study are called sirtuins, and there are seven of those. And they're in all parts of the body, and they do all really crazy good stuff for us.

Okay, and where do telomeres come into play?

Well, they're part of it.

Okay.

Yeah, there are seven hallmarks, or eight depending, These are causes of aging. So telomeres are one of those hallmarks. Other things are like the battery packs winding down, those mitochondria in our cells. We lose stem cells, all this other stuff. But here's the important point. We think, A, that there's a unified cause, a whole upstream cause of all of those things. We can talk about that. But also these sirtuins, they defend against all of those. So while we used to think we'd have to develop eight different drugs to slow down aging, if you just tap into these longevity genes, they take care of everything. Really?

They continue to regenerate good cells, they continue to fight against disease or stress or whatever it may be.

They do. They're really smart. They make proteins that act like traffic cops telling the body how to fend against adversity. And they've been with us on the planet since life first arose.

And seven of them?

Well, the ones I study, there are seven. There are others. There are seven sirtuins and there are three classes of longevity gene, the ones I study, those seven, and there's a couple of others that you can turn on.

Why don't you study the others? Are they not credible enough?

We do, but we scientists, we like to specialize.

Gotcha, gotcha.

But in truth, even though 10 years ago we used to fight with each other. My longevity gene is more important than your longevity gene. It was ridiculous. My worm's living longer than your worm. It was really silly. But now we've realized, most of us admit that all these genes are talking to each other and if you tweak one set, the others will be tweaked too.

Right, okay. So these genes, when you say you study them, what does that actually mean? You're pulling like blood out of different humans and you're putting them in a tube and you're researching and you're like, what's actually happening to study these? Yeah, because I'm a non-scientist. I have no clue what that actually means.

Right.

Is it like rats? Is it humans?

Is it, you know, you've got to come to the lab. You've got to see what's going on. Because it's crazy stuff.

We do anything we can to answer a question. You're cloning humans in there.

You're doing all sorts of stuff, right? It's crazy stuff. So we're driven by the question, not by the. technology. So most labs will say, okay, I'm an expert in rats. I don't give a rats about a rat. I care about answering a question. And our question is, why do we age and what can we do about it? And will that transform medicine? And so what we do, if you came to the lab, you'd see we've got jellyfish growing, we've got mice that are living longer and running on little treadmills. Up in the lab, we have stem cells that we're growing and actually turning them back in time. We can reverse the aging of these Stem cells. Yeah.

So what does that mean? You take a cell from a human, like a sample, like a skin sample, like a blood. Brain cells growing in the dish.

Really? Yeah, yeah, yeah.

Brain cells growing in the dish. So you take it from a living human. Yes. You take a little piece of brain. Yes. You put it in a dish and then you reverse the age of the brain. Correct.

Wow.

Yeah, that's what we do. Now we can actually grow little brains in the dish too.

From scratch?

Well, you start with a network of cells and then you coax them into forming networks and it's like a mini brain, yeah.

Okay, so... And we can age them.

Forwards, make them older.

No.

We think we understand what's driving the aging process.

Really?

And then we reverse it.

So you can create a brain from nothing, a bunch of little cells that come together and create a thinking brain.

Well, I don't know how much of a It'll respond to stimuli. It'll fire, yeah.

And then you can make it older, like Benjamin Button, and then reverse its aging.

Right.

Wow.

I'm telling you, it's crazy. But when I'm in the lab and with my students, for us it's just every day. It's like, Ah, there's the brain.

It's getting older, it's getting younger.

Yeah.

Yeah, yeah.

But now that I'm talking about it with you, it does sound fascinating.

It sounds bizarre. For a non-scientist. Yeah, the other thing that's weird about this profession, anyone who wants to go into it, is that essentially you're an apprentice under me and you work in the lab and you spend a few years learning how to do all this stuff. It's not easy the first two years basically you screw up. But it's weird that to think about it, you get a bench in a lab and some chemicals and you have to make the chemicals yourself usually. And then your job is to discover something nobody else has discovered. It's got to be not just slightly new, radically new, because I'm at Harvard, they don't give prizes for discovering something obvious. Wow. It's got to be shocking.

And if it's not shocking, it's not worth studying. And haven't you discovered like tens or 30 something, 35 awards for new discoveries or something or 35 patents, what do you have?

Something crazy.

Some numbers like that.

You've discovered a lot of new things. Well, yeah, yeah. If I didn't, I wouldn't have a job. There's motivation to always be doing cutting edge stuff. But what drives us, and the reason I think we've been successful, is that we're driven by the question, not by the technology. And the technology comes second. So what I'll do is I'll say, okay, here's a question. We want to figure out why does cold improve health? Or why does fasting not eating improve health? How do you figure that out? Well, then you've got to pull together teams of people. Molecular biologists, biochemists, mathematicians, computer software people. and we get in a room and we figure it out.

Really? So what would you say, and your questions are why do we age and how do we reverse it? Is that the two questions you're focused on the most right now?

Yeah, that's pretty good, yeah.

Why do we age and how do we reverse aging? Do you think, and so you say aging is a disease, is death a disease as well then in your mind? Is it like that just leads into, and can we reverse death? Is that a possibility?

No, not yet.

Okay.

Not yet. So anyone who's had their head frozen, there's nothing I can do for you right now. But we can turn back the clock radically. Just in the last couple of years, we've figured out that there's a backup hard drive of youthfulness in the cell that we can access to reset it. So usually the earlier you start in turning on your longevity genes, the better. We've learned from studying mice and now humans for many years that if you're in your 20s, 30s, 40s, you want.

To start- Turn it on now.

Do it now, 'cause- Don't wait till.

You'Re 80 and then say, How do I go be 60 again?

But most people do. They wait too long.

Why?

Well, 'cause they're in denial that they're mortal. And we used to think that aging was a one-way street. You couldn't do anything about it. We now know from studying twins that 80% of your health in old age is up to you, how you live your life.

Right, your community, your positivity, your thinking, your food, the sleep you have, like all those things, right?

Yeah, and the reason that they work, we discovered, is because they turn on the longevity genes. That's the breakthrough.

Okay.

So now we're artificially tweaking these longevity genes genetically or with supplements or hopefully medicine soon.

Gotcha, but you could do it in more natural organic ways is what I'm hearing.

Well, right now that's what we've got. And even if you just do the five obvious things, things like skip meals and don't smoke and exercise, that'll get you an extra 14 years on average. Really? It's that big. That's not even using high tech.

There's no technology, just like living a good life. So, what are the main things to turning on the longevity that anyone can do without technology, without money, you know.

Science, Yeah, well, okay, so we first of all, don't smoke. That'll damage your DNA, that'll accelerate the aging process.

Does that include e-cigarettes and all these other vaping? Does that also include... Well, I'm a.

Big advocate for putting nothing artificial in your body, including vaping. My mother died from lung cancer, so I'm pretty militant about it. I don't think vaping is as bad in terms of the number of chemicals getting into your body. But we've seen recently it's probably not healthy anyway.

Yeah, yeah. Okay, so no smoking.

That's one. That's one. Next one is don't eat so much. Eat less often. So not malnutrition of course. You don't want to get too thin. But this three meals a day plus snacks is ridiculous. That's brilliant.

In the future. You'll be great.

I need to get rid of that. Yeah, well you're also working it out, but someone like me who's not an athlete, the most exercise I do during the day typically is typing. Three meals a day is too much. Actually one meal is enough for someone like me.

Wow.

Yeah, I'm now 50, so my metabolism is way down. You look like you're 37. Oh, thanks.

That's great, man. We might need to get you a 100. I thought you're like 100 and you're looking at 37.

You've already reversed the aging.

Well, I'm glad I don't look 80, 'cause that would really be bad for your message. Be bad for your message.

Okay, so we got no smoking.

Eating less.

Yeah. Next one would be the obvious high intensity interval training. Lose your breath once in a while.

Lose your breath, what do you mean? Just by like working out?

Yeah, become hypoxic. Tell your body that you're being chased by a saber-toothed tiger or something like that. The reason all of this stuff works in terms of the diet and exercise, it's not that your blood flows more or that being hungry is is just healthy for the body, it's actually that your longevity genes get turned on by these things. And why does that happen? Why does it happen in humans, in mice, even in yeast cells for bread and beer? The reason is that the body senses adversity and says, crap, we gotta fight back. We might die next week without food and we, you know, we're running away from tigers and lions. That's what this survival network, this longevity gene, does.

So it turns it on when it feels like it's in survival mode.

That's it. We want to be in survival mode and we spend our whole lives trying to reduce our adversity.

Right.

Being comfortable.

Right.

Don't be hungry.

Don't be puffed. Don't walk, you know, valet your car.

Right.

Roll your suitcase.

Don't carry it.

For goodness sakes. We've done the worst. No wonder we're getting sicker and sicker.

We're in a world of convenience.

Right.

And it's the worst thing we could do. Really for our bodies in terms of longevity. So those three things.

Okay.

The other two. Let's see what else is there. Oh, the type of food you eat is important. There's a big debate of course.

They say like plant-based is going to extend the telomeres, right? If you're eating leafy greens, that's what I've heard.

Right.

Well, among other things, it's also going to have a couple of really important types of molecules. One are The mono unsaturated fats, fatty acids. You get that from olive oil and avocados. Those are great. And we've just learned that that's a really important trigger for a certain longevity.

Olive oil.

Yeah.

I think when I had Gundry on, he was like, I drink a cup of olive oil a day or something like teaspoons of olive oil. He's just eating it. He's like, I'm trying to get as much in as I can, putting it on everything.

Well, let's get back to that because there's a new discovery as of a week ago that says we think we understand how that works. But in olive oil, there's also what are called the other important component of a plant-based diet are polyphenols, which are the molecules that plants make when they're under adversity, when they're stressed. And I believe that we've evolved to sense when our food is running out. So we get that signal when our plants are so you don't want to eat plants that are like this white, withered, white liquid lettuce you can buy, Californian lettuce. Right, right. You want these colored vegetables that have been a little bit stressed, a little bit dried out. Wine is a perfect example. It's full of polyphenols, one called resveratrol that we've worked on for 20 years. And it activates these longevity pathways really well. Wow. So stress your food, organic. I am for a plant-based diet, but I do eat meat. Occasionally it tastes pretty good, but it's very clear, Dan Buetan is right, when you go to the longest lived places in the world, the Blue Zones, right? Sardinia, right? The Okinawa Island in Japan, they're not eating all meat. And actually we know that if you eat a lot of meat, you shut down some of these longevity pathways. Really?

Yeah.

So you actually, you might look good and grow muscle, and that's great when you're young. You want to find a mate, you want to look good, you want to feel good. but in the long run, I don't think that's healthy.

Really? So cutting down less and less meat, at least having more plants is the way to go.

Yeah, that's, that's what I've done. I was on an Okinawa diet in.

My 20s and 30s, which is what? Just rice and leaves.

And it's a bitter rice. You got to watch out for white.

Rice because it's a lot.

Spike your sugar. Yeah, it's a lot. But it's, it's a lot of tofu, miso soup, green leafy vegetables, dark greens for these. phytochemicals. And then what else was it? There was a bit of fish.

Okay.

Yeah. But.

But also what's important is not a lot of food. I mean, these days, I'm stopping eating when I'm about 60, 70% full. And I'm trying to.

I just never feels full until I'm, like, eating so much that I'm like, okay, I'm full.

Well, you're a young, so I probably.

Well, here's one of the things I think, one, when you eat slower, you start to get. you start to feel it. And I'm the youngest of four. And so as a kid, we didn't have a lot of money growing up in a small town in Ohio and there wasn't that much food. So I learned to grab and just shove it in my mouth. And that became a habit that I've kind of stuck with. And I'm not starving anymore. Like the food's available at any time. I can afford it and I have it all the time. But I think it's reconditioning my mind or a habit or routine of like, I'm not scarfing my face down right now, but it's that mindset of, I wonder if I'm gonna go hungry.

For sure. We all suffer from that. Well, not all of us, but those of us who grew up in regular families, we were told to finish our meals.

Right. Don't leave anything on the plate.

There's hungry kids everywhere. Sisters, right? They're stealing your food. My wife grew up in a very poor family, and even when she was a student, she could barely afford food. She would scrounge and buy potatoes. And at the dinner table, she'll kill me for this, but she will eat like it's gonna all go away tomorrow. But I have to remind her and everybody, everyone should know this, there's always gonna be another meal. There will be another meal, don't worry. But we're conditioned to eat food when it's in front of us.

I think it's a mental conditioning and it's also like, either your body's tricking you or it's your brain or it's your gut or something is tricking you like, I'm still hungry. Even though you've had 2,000 calories in 10 minutes, you're still like, oh, there's food. It's like turning something on. You're like, I want to eat that. I don't know why that is.

Well, yeah. I mean, it's the reason that when our ancestors put on fat and they survived the famine, we don't have famines anymore, thank goodness. But we've descended from those people. So, we've got the genes in our brain that say, eat, eat, eat.

How do you turn that gene off?

Well, you can take certain types of food. I drink a lot of tea and coffee, hot water even, just to fill up my stomach. That works really well.

Okay. Hot water, not cold water.

I just like the feeling of hot water. Cold water isn't as... I actually, it might be something about the heat. I've never thought about it, but for me that's what works. So when I get a little bit hungry at lunchtime, I'll just... I'm basically drinking tea.

Warm water tea? Yeah, you put in like some Interesting.

But it's a fight all the time. You know, I fly a lot and people are bringing...

Nuts and cookies and ice cream.

And you gotta fight it. And it's really hard to fight.

How do you say no?

Well, I do.

I do.

But how do I do that? So I've trained myself to fight it. And the best thing that I do besides saying, Can I have a cup of tea? Is what do I want to look like next week? What do I want to look like a year from now? What do I want to look like when I'm 80?

So you tell yourself that. You ask yourself the question. I think it's also how do you want to feel tonight, tomorrow, next week when you're 80? It's like look like and feel combination is powerful.

Right, because your mind is saying now is important and you've got to train yourself to say tomorrow and the next year is just as important.

That's my life. Yeah.

Right, and that's more important.

Okay, so is that the fourth thing or the fifth thing?

The fifth thing I didn't mention. There are a couple of things. Let's divide it up. One is get good night's sleep.

Sleep and everything.

Yeah. And then surround yourself by friends and people who will take care of you.

That's like the blue zone way too, right? It's like be around a good community, get lots of rest and naps, move a little bit, eat healthy.

Well, these are things that most people should know, but they don't do. So you and I here motivate people to do that.

Exactly.

But the research that I discuss in the book is how to take that to a new level, how to optimize those things and add some science in there.

To reverse it.

Or getting there.

I like this. Okay, before you share that stuff, how did you get into this fascination or curiosity of reversing aging in the first place? Was there someone that inspired you? Was there a moment? Was there an event? did something happen?

Yeah, it was an event that I think we've all gone through. We just forgot about. We learned that there's such thing as death. We don't live in a Disney movie. Right. It's not all happily ever after.

It's not.

It's shocking. When we're four or five, we're told this and we realize it. And we're in denial, you know, oh, no, that's not going to happen. But for me, I haven't been able to get that out of my mind.

Really?

It's cruel, don't you think, that we're sentient beings that. that know that this is all going to end.

We love people, they take care of us, and then they're gone.

Yeah, and I don't want to live forever. I would just like to leave the world a better place. And I think one of the big things that we're missing in medicine is that aging is driving a lot of our sickness. And when we treat diseases, we're treating them far too late. Once you've got, well, I won't say which disease, but take my mother, for example. Let's use her lung cancer as an example. She could have not smoked. She could have done all the things we've talked about. She could have perhaps taken some molecules that we work on and not had lung cancer. By the time she had a tumor that was the size of a grapefruit in her lung, it's game over.

She couldn't do anything.

Right. But we've put billions of dollars trying to cure lung cancer, not prevent it.

If we just prevented it, we wouldn't.

Have to worry about it. Prevention is easier.

Prevention is very easy.

Yeah.

Right?

So how old were you when your mom passed away from lung cancer?

I was 25.

Okay.

And, no, let me take that back. She was diagnosed when she was 25.

When she was 25. When you were 25.

And she went on another 20 years.

Really?

Yeah. But it wasn't really an enjoyable life. It was a-- They took out her left lung.

So was she breathing from a tube.

Or was it like-- She could breathe, but she wasn't. She was always short of breath. There were times when she thought she was just gonna suffocate in front of us. Eventually she did, by the way. That was not pleasant.

Oh my gosh.

That's not something I want to see. Yeah, and no one tells you what it's like to see your mother die. Your parents die. It's horrific.

Wow.

I've never experienced another death, just this one, but it was not pleasant. And we don't talk about it. We deny it, you know. They're gonna drift off into sleep.

That's not what happened to my mom. It's suffering.

It's pain, it's agony, it's suffering, right? Yeah, my mother was turned into a writhing lizard in front of me. All I could do is whisper into her ear, Thanks for being the best mom I could ever hope for. Oh my gosh. That was it.

A couple of minutes later, she's turned blue and choking.

No way. You can't do anything for her. Right, that's it. You're helpless. You're helpless. Anyone who smokes, please, please work to give it up. It's just not a good ending. Wow, were you with her alone?

Were you with family, was it friends? Was it... Yeah, my father and my.

Brother and I, I was also in denial, 'cause I flew from America to Australia to be with her. And you're like, gosh, she's gonna get through this. Yeah, you tell yourself she's always recovered. Last 20 years, she'll pull through. And the doctor pulled us aside and said, we've x-rayed her lung. There's barely any lung left that's working. Oh my gosh. You better say goodbye. And I said, what are you talking about?

Oh my gosh.

She's laughing in the bed. She's fine. And 10 minutes later, she starts choking and fluids building up in her lungs. And, you know, if you've ever seen somebody have something stuck in their throat, that's what it was like.

Oh my god.

You can't get it out.

Can't get it out. You can't. She's drowning. Time lapse.

Maneuver. You can't.

CPR, you can't try that.

Well, I'm running around saying, Help me, help me. And all the nurses are like, It's.

Nothing we can do. Wow.

So that's traumatic. So please, you know, let's try to prevent these diseases as long as possible.

How old was your mom when she passed?

So she was my age when she was diagnosed with lung cancer, and then she lived till 70. Wow.

But she could have, hypothetically, you know, if she didn't get hit by a bus or something, she could have lived a long, much longer life if she.

Didn'T have the cancer. Oh, absolutely. And through my teenage years, I would shout at her, Stop smoking, you're gonna die. When you're in hospital, I'm not gonna come visit you. Oh my gosh. You're only given one life. 'Cause I'm pro-life. Everything about me is we are so lucky to be alive. You know, one in a trillion sperm from your parent, from your dad, and it's you. What's the chance? It is. Don't throw it away. And she was the opposite. She was like, drinking and smoking and I've lived a good life, don't bother me. And she paid the consequences.

Oh my gosh. Not only did she pay it, but you and your family had to go through it also.

Yeah, well, you know, I did go and visit her in hospital when your mum's sick, you know, everything's out the window.

Yeah, of course.

But my father's the opposite. He's taking good care of himself. Really? And now he's 80, perfect health, no aches, no pains. running around the world like a 25 year old.

Wow.

So that that's the dichotomy there. If you do the right things, it's a very different ending.

Now, were you already into anti-aging when she was diagnosed? Or was it before, way before that? Was it shortly after that? Or when. When did you become kind of obsessed with being the master of anti-aging?

Well, I've got an obsessive personality. Yeah, I think anyone who's become at the top of their profession and has to be obsessed with something. They're not normal people. They're not normal. At age four, I became obsessed with it, actually. Four?

Yeah, it's four. My first memory is four. I don't even know.

Well, this is my first memory.

Really? What was it? Seeing your mom smoke and be like.

I don't want to be like that. Well, that was that. Yeah, you know, in the 70s, early 70s, when I was a kid, the smoke was everywhere. I couldn't stand it. But that was not really my motivation. It was that my grandmother who helped raise me, told me, Everybody's gonna die, and so are you, and so is your cat. And my grandmother was brutal. She didn't lie. She told it as it was. But she said, Now that I've told you that, you know, I hear am I crying. My cat's gonna die.

Santa Claus isn't real. My cat's gonna die.

It was my cat that was the problem.

Oh my God, you love this cat.

Yeah, 'cause she said, oh, your cat's gonna die before you're 20 or whatever. She said, Now that you've realized that, here's the lesson. Make the most of life. Do your best to make humanity the best it can be and don't waste a second. And that was it for me. Okay, I'm gonna go for it.

But when did you actually start researching? Okay, now maybe you had this positive mindset. I'm gonna make the most of every moment. I'm gonna enjoy my life. I'm gonna learn quickly and not be stuck in the these painful moments. What was it like, middle school, high school, where you're like, oh, mitochondria and.

Telomeres and, you know? So I was a pretty average kid. I liked to have a lot of fun and I didn't really take care of myself. Actually, you'd be surprised, I was pretty chubby as a kid. Really?

Yeah.

But I got to college and two things happened. One was I started studying. Where were you in school? I was in Sydney. In Sydney. Okay. So I went to, there aren't that many choices in Sydney. I went to It's called the University of New South Wales, like the MIT of Boston. So I was there and I wanted to get a degree in what we used to call genetic engineering. And I thought, that's a cool thing. Everyone's going into computing, I'll do something. Because I've got also the personality that I don't like to be told what to do and I like to be different.

You'd be unique, one of a kind.

Yeah.

Yeah, I do.

Me too. I was a big dumb jock who never drank a sip of alcohol in college. who learned salsa dancing and guitar, who is in choir, in the musical, like I was, whatever you thought I was gonna be, I was like, I'm gonna do the opposite. So we have that in common.

Yeah, probably your parents learned they had to tell you the opposite of what.

They wanted you to do.

Exactly. So I went to college and I realized two things. One was, if I'm chubby, I'm not gonna get a girlfriend.

Right.

So I started working out.

Survival.

Survival mode. I ate carrots for a month and shed 15 kilos, whatever that is in pounds. Got a best body I would have dreamed of. It's long gone. That was one thing. So I became healthy.

Yeah.

And I've been this weight ever since, basically haven't changed. It takes effort.

Yeah.

And the second thing I realized was that I think I could make a difference in the world. And I was playing cards with friends. We did a lot of drinking. They did a lot of smoking, typical college life. And there was a moment where somebody was talking about old age and laughing at old age and making fun of old people, which we do sometimes as kids.

Yeah, we were young.

Yeah.

How old they are.

And I had an epiphany. I think I was 18 years old and I said, Do you realize everybody? Hold it. No cards, shut the fuck up. I've got something to tell you. I've just realized that we are probably the last generation of humans to live a normal lifespan. 'Cause there's gonna be a breakthrough and we're gonna miss out by one generation.

Oh my God.

Out of the, how many 100,000 generations leading up to us of primates, we're the last ones. We're the last ones.

We're gonna die at 100 or 80 or whatever.

Right, and our kids are gonna live to 130, who knows what.

And their kids are gonna be 160.

Yeah. So then I thought, hey, that's what I want to do. I want to make that future be a reality in my lifetime.

Wow.

Isn't it sad if it just gives us about 50 years to be born? How much farther you could extend life, right?

Yeah.

I didn't realize how quickly the science would go. I thought that I'd probably be lucky to see a little bit of change in my lifetime.

Like 5, 10, 20 years, maybe more.

Well, we already got 14 just in what we talked about.

Right.

But the kind of breakthroughs that we've made now, you know, I get criticized for looking too far into the future because I'm supposed to be a Harvard scientist. But I think another five, ten years is easy. Look at my dad. He's doing all the right things. Also taking some molecules that we've worked on in my lab. They're not doing any harm. I hope that he makes it past 100. It's not a clinical trial, clearly, with one subject. But he's a role model for what life can be and should be like. Right.

So now is this molecule, the same molecule that you worked on 10 years ago that got a lot of credibility and then was debunked, I guess, by some researchers and then now in the last week has come back to be verified as true?

One of them, yeah. So resveratrol is the red wine molecule. It's one of these polyphenols that plants make when they're stressed out. And that we found, at least we thought that when you take this molecule over many decades or as a supplement, you'll be protected against a whole variety of diseases, including obesity.

Really?

Yeah.

Is that where everyone says, like, drink a glass of wine every night or something? It's gonna make you live longer.

Well, that's basically because of me, but. There's other research, of course. Other people have studied red wine We found that people who drink red wine tend to live longer.

Live longer, gotcha.

Dan Buetner will tell you all about the blue zones.

Right, so this molecule, is it something you discovered 10 years ago or you started researching 10 years ago?

Well, so remember these longevity genes, they make proteins that tell the cell how to survive. And we can turn on the production of these proteins by being hungry and exercising and being out of breath. But we wanted to do it artificially because if you're an older person in a wheelchair or you're like my mom.

And she's- you-'re not doing hip workouts at 90.

Yeah.

You need a drug. You can't just expect them to run marathons or go hungry. So we wanted to figure out how does fasting, how does exercise work? That's another important question, couple questions. And we found that this sirtuin number one, there are seven, number one was very important. In mice if we turned it on, we can make mice with extra genes.

By the way, in the lab.

You can make them. We make mice. From scratch.

Well, from stem cells. From a cell, you can turn it.

Into a moving mouse.

Yeah, that's easy.

That thinks and breathes and has a whole heart. Come to my lab, you can make a mouse.

What?

We can make them glow green if we want.

It's not that hard. You can take cells and they just kind of like form together and turn into a mouse.

Well, we need another mouse to gestate it.

But it's, yeah, it's pretty easy these days. these days.

Okay, this is crazy.

I'm coming, I'm gonna check it out. You can take a skin cell of a mouse, turn it into a stem cell, make a sperm, make an egg, fertilize itself, and make a mouse out of it.

What?

That's nuts. Anything's possible these days. Wow. So we engineered a mouse to have more of this sort of two in one gene. Yeah.

And it was protected against a whole variety of diseases. Really? Were you injecting with disease to like test that or just natural environment diseases.

So we have a lab where we-.

It's like other mice have the disease.

We let them age. Yeah. And that's the main thing. We have a lot of old mice and we test them if they're frail. We look at their strength, put them on treadmills, test their memory. This is crazy. We've got this whole floor in the building- Mice. Of mouse testing machines.

Shut up. How many mice are in the lab?

Thousands? Well, I don't want anyone to be upset because we do have a large number of mice. Okay. Our goal is to make them healthy. Unlike a lot of other labs.

You're not trying to kill them like most labs.

No, no.

You're trying to say how can we.

Keep them as healthy and long. And our mice live longer. So we're one of the few labs where we do that. But yeah, so this sort of 2 in 1 gene, it makes a protein that helps the cell. So we found this red wine molecule. just coincidentally turns it on. So if you put the enzyme, we can put in the little test tube where these little test tubes, and we put in the protein, and we can test whether it's more active or not by how much it glows or fluoresces. Okay. And then we tested thousands of molecules. And the one that worked the best was this one from red wine. It made it glow really brightly, fluoresce. And that was the beginning of this story where we found a molecule from red wine. that turned on our body's defensive enzyme. And that was great. We put it onto yeast cells. They lived longer. I did that experiment in my dining room, actually. You can make yeast cells live longer.

Oh my God. That's crazy.

We fed it to mice, and they were much healthier. They were resistant to obesity and diabetes and cardiovascular problems. It basically made mice immune to a high-fat Western diet.

Wow. they could eat whatever and it wouldn't affect them.

And they lost just as long as those that were.

They burn the fat quicker.

Well, they were actually still fat. That was the crazy thing. But fat didn't. Didn't hurt them. They were immune to the effects of being fat. Wow.

That's amazing. Yeah. Okay.

But. But then. And this is the one that my father started taking about a decade ago. Same as me. But here was what happened in. That was 2003 to 2006. things were great. We started making better molecules. We made thousands of them. They went into human clinical trials, put it on the skin of patients with psoriasis. They were actually, it was a pill, and the psoriasis got better.

No way.

Yeah, we were on track to having a medicine for aging and diseases that are related to aging and inflammation.

Wow.

But then everything fell apart.

Why?

So in 2010, a couple of companies published scientific papers that said, it's all wrong. That this molecule, resveratrol, does not activate this enzyme. This fluorescence that we're looking at in this test tube was just an artifact. It was fluorescing for other reasons. It wasn't real. And yeah, my world fell apart. The company stopped working on it and it was hell.

You stopped working on it.

Well, we didn't. Well, for about two weeks, I stayed in bed. It was horrific. I went into mild depression, my lab, didn't know what to do. I had friends calling me, well ex-friends, who called me and said, you know, I'm really sorry and didn't hear from them again. It was a tough time. And when you're, you know, and this is what I built my career on, I was known in the world for this. And then it went away. And if you're a scientist and you lose your reputation, you're screwed because you're relying on grants and your colleagues opinion of you to give you the money. To give you those.

Their endorsements, their recommendations, things like that. Right, so if no one's recommending you anymore, no one's giving you money.

Yeah, grants dried up. I had 20 people, vibrant lab, world-leading science, top of the world, gonna make this medicine, bam, most people left. No money, four people, tiny little lab. Even people in my lab said, I'm out of here, this is crazy. you're full of it. And there was one student who I had, his name is Basil Hubbard, and he said, you know what? There's something to this. I'm not going to give up. Wow.

And.

But the other people in the lab, one guy in particular was really mean. He just said, you're working on this BS stuff, this resveratrol stuff. But he figured it out. It took him three years to figure out the intern. He was a PhD student.

Okay, I got.

Basil and just through grit and stubbornness and genius he figured out that it was real and we published in 2013 three years later that there was good evidence that we were not wrong. So okay, take a deep breath. I'm swimming. I'm not drowning anymore.

This is three years of like depression or just figuring out how am I gonna get to my life, my career, everything back on track?

Right, right. I was so mad with the world.

I'm sure.

I said it.

You know, through everyone, I can't trust anyone anymore.

Well, it was that because I devoted my whole life to this. I'd barely taken a weekend off in my life.

Yeah.

And to have that happen, it was like, oh, you know, I could have retired at that point.

How did you recover?

Well, so the problem was I didn't want to die not knowing the answer.

Wow.

Needed to figure this out. And knowing that I was wrong was still better than not knowing it all. So we tried to figure it out.

Because it's better to be like, okay, I'm actually wrong. Here's the proof. Here's the science. You can live with that is what you're saying.

Right.

Knowing the truth. And then, okay, how do we solve it? What's the new solution? Right? Where do I go next?

Yeah, and we actually had evidence that we weren't wrong. So that's why I got out of bed, went back to the lab and said, Let's figure this out. Let's do some key tests that'll tell us either way if we're right or we're wrong. And it turns out we weren't wrong. And there was this study you referred to that came out a week ago that said, You know what? That mechanism that you discovered actually is really important for being activated when you're fasting, when you're hungry. What happens is when you deplete fat, let's say you're hungry, you haven't eaten breakfast, you'll melt away some of the fat and you'll generate what are called free fatty acids and some of them we can get from plants from olive oil, monounsaturated fatty acids, the good ones. A lab discovered that the way resveratrol works is actually just mimicking those unsaturated fatty acids that we already know are good for you. And Dan Buetner in the blue zones would tell you, from the blue zones, would tell you that these are what leads to long life. Wow. And so it turns out resveratrol, if this is true, is basically mimicking gobs of olive oil but without all the calories. So my father and I, you know, maybe we've been doing the right thing.

So he's been doing, your father's been doing this for 10 years. Even though people try to say this isn't true, this is stupid, it's not actually doing anything, but he's been taking it consistently.

Right.

Well, he's a scientist too. Everyone in my family is a scientist, including my wife. And people say, oh, are you testing this on your father? No, he's a scientist. He can read this stuff for himself, and he's the one that made the that he believed in it. And yeah, I'm glad that he did because so far so good. Wow.

Okay, so that just happened last week. So 10 years you've been waiting for this to be like proven again.

Right, and we've always predicted, I've always said, resveratrol isn't the big story. The big story is A, can we make a medicine, which we're still trying, but B, we call it the endogenous activator. What's in our own bodies that resveratrol is mimicking? And it's these monounsaturated fatty acids that come from when we're hungry or if we eat these healthy plants.

Wow. Okay. That's pretty exciting.

It's damn exciting, but it's not as exciting as I thought it would be. Because in life, it's always an anticlimax, right? You think, I can't wait until this in my life happens, and then it happens. You think, yeah, but tomorrow I've got something else to figure out. Really, I mean, that's just my personality. Are you like that?

I'm very much like that. I remember my whole life I wanted to be an All-American athlete. Like, this is one of my first memories, is like watching a football game on TV with my dad and him like continuing talking about these few guys on the Ohio State football team who are All-Americans. And you know, you want your dad's approval and he's talking about a few guys on the team. and I'm like, I want to be an All-American athlete. You know, if these are the best of the best, that's what I want to be. And all I did was obsess about being the best athlete I could be and becoming an All-American. And I remember I was in the Decathlon National Championships 2005, and there's 16 athletes that go to the National Championships per each event. But the top eight are All-Americans so you got to be in the top eight to qualify as an All-American and the decathlon is a two-day event. First day, I have a pretty good day. Second day, I struggle a little bit, and it gets down to the last event, which is the 1500. And my coach is like, okay, you need to beat these two people, and if you get in front of them, you're gonna make it. And I literally cross the line with, like, one of the guy next to me that I needed to beat who was like neck and neck and I didn't know who went in front of the other. And so I'm waiting for like 30 minutes for the final results and they make the announcements of the final eight and I got eighth place. And I remember feeling like there's so much excitement. I'm on the podium, I'm like holding the trophy. I'm like, I did it. My childhood dream came true. And then probably 20 minutes later, I was angry. I negative. We're all having dinner celebrating and I'm like, I don't want to be around anyone. And I didn't know why that was. But that's like with every accomplishment I had in my teens and 20s, I kind of had that same nature where I was just like, well, it's not good enough. I need to go after the, become a professional athlete. I need to do it twice.

I need to, I don't know why that is.

Well, that's why you and I are sitting here. I think we never rest. Exactly. Yeah. So anyways, but We have a lot in common. I'm like a scientist.

I'm gonna train you.

Yeah, exactly. We're gonna build a rat from scratch. It'd be amazing. Okay, so this paper came out or this finding came out a week ago. You had a nice moment, but then you were like, well, on to the next.

Right, right. I don't know why. I think it's because I was hangry at the time on a plane drinking tea.

When you read it or when you just found it?

Well, actually, so the guy that trained me, so I went to MIT after Australia. Lenny Guarente, he taught me how to be a world-class scientist. And he and I have been good friends, but frenemies kind of butting heads scientifically, but we're very close. Anyway, like all mentors, I look up to him. His opinion of me matters. And it was he who wrote an email to me last week, and the subject line was, Wow! Exclamation point. And in there was this paper saying, Dad, you were right. Yeah. But he didn't write anything.

That was it.

Wow. Those three letters. --And the paper. --And the paper.

That's it.

And you knew what it meant. Yeah. --That was it.

--Was he on your side after the whole paper came out seven years ago.

Or eight years ago, I guess? --Yeah. I got to give him credit. He never gave up on me. --He stayed with you.

--Yeah, but he's been through held to.

This feels really tough.

Isn't that interesting? The people that have gone through the most crap, ups and downs, they're usually the ones that stick with you when you've got some type of public shaming.

Yeah.

I noticed that as well. That's crazy. So that's good. So you had a few people that kind of stuck with you and said, Hey, listen, like, this is gonna hurt for a few years, but eventually you're gonna do something else and then people.

Are gonna forget or they're gonna move on.

Yeah.

Well, he's not that touchy-feely, but. He was very supportive and, you know, we're both the two guys that drove this field of sirtuins, these longevity genes. So we're comrades.

Gotcha. You're frenemies, but you're like, we need each other to push it forward and validate our research.

Right.

Your enemy is, you know, my enemy.

Right. Okay. It's interesting. Now, you told me a story before we got on about how you were homeless for a year in the UK. UK. Is that right?

Yeah.

Can you tell me how did this happen? You're in Sydney in school, and then you moved to the UK and you're, what, sleeping on the streets, eating rats that you made from scratch or something or what?

Kind of with it. Without the rats, but basically that kind of food. Yeah, this is. This is a story I haven't ever told anybody.

Why not?

It just doesn't come up. I don't. I don't know. I'm not the kind of guy that boasts about this kind of stuff. But it's so my accent is a little bit Australian, a little bit UK. And so I spent a year and a bit in Wales in Cardiff in the middle of winter.

So Cardiff in the middle of winter. My ancestors are from Wales.

Are they?

Yeah.

Do you know any Welsh? No, I don't. Crazy language. Crazy. Tried to learn a bit, but they sing their sentences, so that's why my voice is a bit more like that. Anyway. that's not important. What's important is that I like to take a lot of risks, especially when you're young, you've got to take a lot of risks in your 20s, 30s, go for it. So when I was 23, I said, I'm going to go to the UK and do some of my PhD research. And there was one guy in Cardiff that knew how to do some stuff. So I said, I'm going to come and work for you. He said, Great, I got no money. I said, that's great, I got no money either. But I'll figure it out. But I had a few thousand dollars.

Yeah.

Like, you know, from delivering pizzas.

Sure.

And so I bought a ticket, flew over there, stayed in his house for a few weeks, but he said, you can't live here. I've got my own family to deal with. He was a bit of a grumpy guy anyway, and I didn't want to live with him. So what I figured out was, if I go to the bar, the pub, we'd call them, at night and play games. So they used to have these little consoles where you'd play trivial pursuit, and you'd make friends. And after they were drunk, I'd say, hey, have you got a place? And they'd say, we don't have a bed, but we've got this bean bag if you want to come around. So I'd do that and I'd stay there for a week or two, and then I'd have to go find another place.

Wow.

Usually. And I was eating these cans, these tins of tuna.

Tuna.

Yeah.

Bumblebee tuna. Or staple. Ramen. So for a year you did this.

Yeah.

So you had no. You weren't paying rent anywhere for almost a year. Were you making money as well? Like a little side money or.

I think I still got us. It was fifteen thousand dollars a year. But the problem was that the pound versus the Australian dollar was twofold.

So I.

My dollar was half the value. So it wasn't enough to pay rent.

You were just like, okay, I gotta eat food. I gotta get the bus. I gotta do whatever.

Yeah.

Yeah. You know what's funny? Gosh, we have a lot in common. the one time that I almost slept in the streets. I was in Philadelphia. I had no money. I went to a conference and I met someone from LinkedIn who was like, you got to come to this event. You're going to meet some great people. I was probably 22, 23. I just got done playing professional football, trying to figure out how to get a job, how to find some connections. And this guy I met named Ben Stern was like, come to Philadelphia for this conference. You can stay with me on the couch. So he ends up, I stay in a hostel for two nights and he's like, can you stay with me the last night on the couch? Because I only had enough for two nights in this hostel, it was $14. And I took a Greyhound bus to get there. It took like 30 hours. It should have been like six. And the last night, I'm like, okay, tell me the address. Let me know. I'll meet you at your place and I'll crash on the couch. and his phone dies, so I never get his address, I never get a hold of him. And I'm in the hostel, I didn't have the money for the hostel, and they want to give me a bed. So I'm walking around the streets of Philadelphia with my suitcase and a jacket on, and it's like 3 a.m., 3:30, and I'm like, what am I gonna do? There's benches, maybe I'll sleep on a bench, 'cause my Greyhound bus was leaving like later that next day. I don't drink, right? But I was like, for some reason, I feel like if I go into a bar, I'm going to meet someone and I'm going to build a relationship and maybe they've got some couch or something. And I did exactly what you said you did. I met some people there playing darts. I went in there and I was like, let me play some darts with you. And I just like built a relationship. After 30 minutes, I said, hey, I don't have a place to crash. Do you guys have like a couch or something? And they had a futon that let me come in there. I let myself out in the morning.

And that was it.

But That's how you sleep not on the streets and you meet friends at bars.

Yeah, it's a tip to everybody who's watching.

That's it. That's how you survive.

That's how you survive. Go to the bars. Yeah, so Benjamin Franklin said he slept on the floor and knew that he could survive.

If you can get through that, then.

The rest of your life is easy. Just sleep on the floor.

Yeah.

No pillows, no sheets, sir. Yeah, and that's how I've lived my life, at least up until fairly recently, which is I know what it's like to be poor and not have anything. So I'm gonna go for it, 'cause the worst that can happen is I just go back to that.

What was the biggest lesson you learned about yourself with a year being homeless?

Being homeless isn't so bad. It's a lot of fun. But also that I have grit. You know, I grew up in a pretty easy family. I was in the suburbs of Sydney. My parents weren't wealthy, but they certainly weren't starving. I didn't know if I had what it took to survive. So that was my real test.

You needed that experience.

Yeah.

Yeah, and everything after that was easy.

Yeah. Well, except for being like debunked, fake debunked by your, you know, researchers and peers.

Physically, I can handle anything. Mentally, I'm not that strong.

Really?

Well, I try.

Do you think this made you more emotionally, mentally strong going through this, like, worst case scenario? for your career?

I like to think so, but I still get beaten up even, you know, in my 50s now.

Really?

We just had. I just had 10 years of work with 15 Labs collaborating with me, guiding them, and it's 55 scientists. We submitted this research. We wrote it up. It took a year to write. We've sent it to a journal and as a scientist, your work gets reviewed by your peers anonymously. So they can write whatever they want.

They put their name on it, yeah.

So what happened just before the holiday break was there were four people who wrote comments about our work. Three of them said, this is paradigm shifting, brilliant, got to be published, will change the world kind of stuff.

And you didn't know who those names were?

I didn't. There was one that wrote, this isn't exciting. We already knew this, which is not true. And the journal said, We're gonna side with the one naysayer.

Oh, that's the worst.

That really was a blow.

That was crazy.

I felt like someone hit me in the head with a baseball bat.

Isn't it crazy that we also focus on the one negative when there's thousands of positive reviews of a book or something, and you see one negative, and you're like, why?

I got rejected. So that's 10 years of work.

Oh my gosh. With 15 different labs working on this, is that right?

It was everything. And I had this in my mind that we're going to get it into this world-class journal. And I talked to the journal and they said, we're waiting for it. Let's do this. And that was the future. It was supposed to be this and nothing else. And then to have it rejected. And editors usually they go with the majority. majority rules.

Why would they go with one?

I still don't know. That's what it doesn't make any sense.

Is there a way to resubmit or.

We're gonna challenge it. So I'm writing up a defensive letter, an appeal, as we call it.

Gosh.

But yeah, I thought I was resilient and nothing could. Could get to me, but that did.

It's kind of like being a Olympic gymnast. It's like you could have your best performance, but if one judge didn't like the way you pointed your toes.

Yeah.

And they give you a 9.2 as opposed to a 9.9, you could lose based on an opinion of one person. Yeah.

I don't like that.

That's not like, I thought science is like black and white.

Oh boy, there's a lot of politics. Really?

But it's like if you've got, here's the proof, 15 labs, independent case studies, and like triple checking, I don't know.

That's how it's supposed to work. That's why this was such a blow. Because everything I thought about how science worked was thrown out the window in this case.

Why do we even have science if--.

It'll get published, don't worry.

But I mean, if you can't prove something through science, why do we even do it then? It seems like-- well, we can prove it to me.

Well, what'll happen is either we'll get it, we'll get this appeal, and that'll be great, hopefully. Cross your fingers. But we're going to have to rewrite it potentially for other journals, which will take us a long time. So the world won't find out about this for a while.

Can you just write it yourself and publish it on your website and say, this isn't published in a journal yet, but here's all the research, here's all the proof, here's the study.

Well, you can. It's just not credible. Right, no one will give you credit for it. Now there are what are called preprints. pre-publications. So now we can put our work online. And in fact, you can go online and see this work. If you go to a place called bioarchive-rx-iv and type in my name, you'll see that the work is publicly available, but most people don't see it and the press can't comment on it. Got it.

But I mean, how many of these journals have published things that people said, yes, this is true, but it wasn't true? You know what I mean?

Yeah, quite a lot. Probably a third of what's published turns out to be wrong. But that's true for all science.

That's every- Why do they publish it?

I mean, it's like- well, we do our best, right? We can always be wrong. You know, even Newton was wrong. Even Einstein was wrong until quantum mechanics overturned it all. We're all wrong.

All science is wrong.

We're right until we're wrong. We are, but those steps along the way are stepping stones to more knowledge. But science goes forward and backwards in little steps. But overall, it's forward. It seems exhausting. Gosh, I just want to hang out with the rats.

Yeah, it is. I mean, you try not to make a mistake.

You try not to conclude things that are wrong, right? Because that'll damage your reputation. Fortunately, so far in my career, that hasn't happened.

That's why it takes so long to do the research, right? It's why it tastes So many trials, so many rechecking years and years.

Well, most labs don't spend 10 years on a project. You'd spend maybe two or three. This was the big one for me.

Oh my gosh. This is sad.

This was figuring out why we age.

Oh my gosh.

Oh, that's not important.

Was there anything new in there that you discovered in the last year that hasn't been out yet, that hasn't been talked about?

Yeah, well, it's in my book, but other than that, that might be why the journal's angry that some of it ended up in the book. But maybe I jumped the gun. So what we think we've discovered here is that cells lose their ability to stay young because they lose information.

Because they lose information.

Yeah. So there are two types of information in our cells. One is the genetic information that we get from our parents, of course, DNA. But there's another level of information that's just as important, but we just don't talk about it. It's called the epigenome, which is the instructions to tell the cell which of those 25, 23,000 genes to read. And if you read the right ones at the right time, you'll be a nerve cell or a skin cell. Because you don't want to read all 23,000 at once. That doesn't work. It doesn't work. So the epigenome is like the pianist that plays the piano. piano. And what we think we've figured out is that aging is that the Pianist becomes demented.

Demented.

Just can't play the tune right anymore. Interesting. The wrong genes come on.

What is that? What is that called? The Pianist. What's that called?

The demented Pianist.

What's it called?

The Epigenome.

Epigenome. Okay, so the Epigenome becomes demented.

Yes.

Loses function in some way.

Right.

And we can cause that to happen. One of the main reasons that it happens, we think, is chromosomes break every day, a trillion times in our body every day. And in the process of having to open up the DNA and fix it and put it back together, the epigenome gets messed up and we lose the ability to read the right genes.

So how do we stop it from breaking?

Well, you can't always prevent it. Start by not smoking. Start by not getting burnt by the sun. Really?

Yeah.

Don't be in the sun for too long.

No, no. I mean, we know that age is your skin. Any Australian will tell you that.

What about like, what's the amount of time we should be in the sun without aging? Or does it always have sunscreen on at all times? Isn't that chemicals that affect this?

I mean, yeah. There are some people who will tell.

You that zero is the best.

Zero sun?

Well, that's what some people say.

Isn't vitamin D supposed to help you live longer, too? Well, yeah, they would say say to take a supplement instead. But I'm not sure.

It's human nature, right?

Like, sun, for me, makes you feel good, a bit of UV. But you don't want to overload the body. It's very easy to overdo it. So 10, 20 minutes. When your skin's starting to tingle, don't get red. But in Australia, we used to pull.

Bars of skin off our backs. Blisters, right?

Yeah. Yeah.

So I've only been burnt maybe once or twice. twice in my adult life for good reason.

Don't say this time in too long.

Right, right. Unfortunately it ends up, you know, you look white and pasty, but for Caucasians anyway.

Right.

But that's the price you pay. If you suntan a lot in your 20s, by the time you're 40 or 50, you will look about five, ten years older.

Okay.

Now it's not all about vanity, but skin cancer is also an issue. In Australia we learn a lot about that.

So you can be in the sun, just put protection on, is what I'm hearing. That's right. Or just stay inside all day.

Yeah, no, put protection on.

I mean, it's like enjoy Mother Nature. You can go to the beach, you can go on hikes, just wear a hat, put sunscreen on your face, your arms, your hands, right?

Right.

Okay, just me.

Okay, cool. Yeah, yeah, you gotta go outside. for sure. I mean otherwise what's life without it?

Okay. Now I just did this trip to Poland with Wim Hof where with a group of guys where we did this intensive breathing and ice therapy training where we were in the ice for 10 minutes up to our neck breathing and exposing ourselves to the cold. We also hiked four hours in a mountain. There was about 50 miles an hour wind at the top, -22 Celsius, with no clothes on, just shorts, hats, gloves, and shoes. So exposing our legs and our chest and our face to the wind and the cold, pelting us with hail essentially at the top. How important is heat therapy and cold therapy to aging or anti-aging?

I want to hear all about this story. This sounds fascinating. fascinating. We would definitely tell us more about that. But yeah, so when I started writing the book, my editor said, you, got to talk about this cryotherapy and also sauna. That's not science, can't be real. So I looked into it and we'd also actually, I must admit, we'd done some work on cold already, one of these sirtuin protective genes, not number one that I talked about, but number three, responds to cold and actually turns on healthy production of what's called brown fat. So the more I looked into it and the more I can pondered my own research, I thought maybe being cold does help your health. And so I write about it, but I think that the data, it's not as strong as fasting and exercise, but it's believable that what you're doing when you're cold or actually when you're hot is turning on those protective longevity juice.

Yeah, yeah.

I mean, not internally. You're not going to freeze internally in a cold, but on your skin you're gonna, and just under your skin you're gonna have what's called brown fat, which is full of energy producing and heat producing mitochondria, the battery packs of cells. And those mitochondria are really dense and it's one of the reasons that they're brown, not white fat. And the brown fat, it's not It's not like normal fat where you're just storing energy. It's actually metabolically active. So it's burning energy. But it's also seemed to be healthy because it's secreting these little proteins that tell the body to stay young. We don't know what they all are, but there's a lot of evidence that it's doing it. Stay young. Well yeah, so brown fat is found mainly in babies.

Wow.

Because they can't shiver.

Little babies, did you know that?

I don't know.

Why can't they shiver though?

I don't know.

It's weird.

How old do you become until you can shiver for the first time?

I don't know. I'd have to guess. But newborns don't shiver and they have to use this brown fat. They're full of it. But as we get older, we lose it. In fact, when I was, you know, 20 years ago when I was just starting out, people thought there was no such thing as brown fat in adults. And then they did PET PET scans and found that this brown fat was mostly in people who were cold and experiencing cold and found across the back mainly. So you can recreate brown fat as an adult?

Yes. Or beige fat.

You can turn your white fat into brownish fat by being cold.

Do we know how much cold therapy you need to do? Is it once a month? Is it once a week? Is it daily? Is it for a certain amount of time?

Well, we're still figuring that out, but it seems like the more the better, unfortunately. So what you were doing sounds perfect.

So like every day doing a cold shower or an ice plunge for a couple minutes a day or just something like that helps generate brown fat, which is a layer of mitochondria, dense mitochondria under the skin, which helps you burn more fat. Yeah, is that what it is?

That's a good way to put it.

Okay.

It's designed to keep you warm, but it also is telling the body, Hey, times are tough. We could freeze to death. Adversity, right? What doesn't kill you makes you live longer.

Oh, that's a good one. So put your body through pain throughout your life as consistently as possible. Like controlled pain, right? Going in a sauna for 15 minutes and pushing an extra minute, like that feeling of adversity, going in cold, working out hard, doing something where it's a, you're not gonna kill yourself or hurt or break a leg, but it's like discomfort. Is that what I'm hearing?

That's the most important lesson. We call it hormesis. And it's basically your body will be complacent if you don't tell it to work hard. And the problem with our society is everything is designed to be comfortable. Comfortable. That's what we strive for. You know, I was coming here flying out and I'm looking at all the roller bags and thinking, and I'm carrying my two bags here. and I'm thinking, should I put it down? No, I'm gonna walk with my bags, because that's what people used to do. But, you know, these days everything is all about comfort. Constant food, don't exercise, don't be cold ever. It's crazy.

We're killing ourselves.

We're accelerating our aging process. So we've got to get out of that comfort zone.

We're killing ourselves by being comfortable. Right. So is there too much, like if I'm cold therapy, and hot, and fasting, and doing a HIIT workout, is there such thing as too much discomfort in your life that will start to age you?

I don't think so.

So I could fast, be in the cold, and the heat, two minutes of sun, do all these things in a day, do it consistently, carry my bags everywhere, and you think it'll make me younger?

I think your rate of aging will be slowed down dramatically. Skip a meal or two a day as much as you can. Yeah, I mean, there's no question in my mind that this would work. Give you an extra at least 15 years, maybe 25. It's not rocket science. If you do that to a rat, if you give it cold or you actually give it less food, it starts to... If you come to my lab, you'll see mice. We've got mice that are on a regular diet. They can eat whenever they want.

Food just laying around, just eat as much as you want.

And those are not fat mice because they're on a lean diet. The ones we give the high fat diet, they die 30% faster anyway. They age rapidly. But let's say even if you're lean like you are and eating well, but you're eating a lot, right? Constantly. If we do that to a mouse, they will age at what we call the normal rate. So they'll be two years old, they're getting frail, they get gray hair, they're looking old, and then they'll die about six months later on average. The mice that are on this calorie restricted diet that either get less food in total or only eat for a few hours a day, they're running around the cage, no gray hair, they're super active, they stay young.

So don't eat.

Well, you gotta eat.

It's fasting. It's what do you like? Intermittent fasting. We do like the 24 hour fast. like a three-day fast. What do you think is ideal for most people?

Well, yeah, scientifically, I think going for three days is great. So scientifically, Peter Attia hats off to him. That's his profession. He can do that.

What's the. What's the prolong or what's the diet? What's this guy?

Peter Attia.

Yeah.

I don't know what his diet is.

Does he have a diet? Does he have, like, a program for this or.

No, I think so. He's. He's a doctor who's experimenting on his body in severe ways and three days is like what he goes for a week without food He just drinks water.

And Skin and bones though, right? Yeah, it's probably not the best for high performance of life no, no, no.

If you're an athlete forget it so.

What if you're an athlete if you want to work out and do hit training. Yeah, what what is you think is scientifically Right like one day fast and then intermittent fasting and skipping meals?

Well, so I get asked this every day. And the simple answer is do as much as you can and the more the better in general without losing your energy. But the other fact is that nobody knows the true answer. Anyone who says this is the way to do it, then I'll know, is BSing you.

Because everyone's different and we all have.

Different needs and different bacteria in the gut, different energy levels, different jeans, different lifestyles, different professions. And so for someone like me, I'll tell you, what works for me is, so I'm often sitting probably for half the day. I got a standing desk, that's a start.

Right.

You're not working out?

No. I work out once a week for a few hours, that's about it.

That's it.

As much as I can do. So for me, what I do is I very rarely eat breakfast. I'm not hungry in the morning anyway. I try to skip lunch with my cups of tea. I would say I'm about 70% successful. I might have a little nibble of something in the afternoon because I can't focus well.

Right.

But then I have a normal dinner. I go out to dinner and I'm living normally.

Yeah.

That works for me. And I think for an athlete, at least skipping one meal would would be good.

It'd be good. And then maybe one day a month not eating or something, right?

Yeah, that sounds reasonable. Going for a whole week though.

Yeah, 24-hour fast could be good once a month.

Yeah, one thing though about that three-day fast. I've never done it myself, but what happens we know is that it kicks in what's called the super cleansing autophagy.

Pathway, which kills the bad cells and.

Gets rid of the bad proteins that have accumulated.

Three days.

You need to go for three days to really get the deep ones, unfortunately.

You've never done it though, huh? But you don't need it. You look like you're 30. So you're fine.

Maybe I could be 20, who knows? Yeah, I'm just a schmoe. I'm not as... I don't have the willpower that you guys, I couldn't go hiking in the snow.

Right, I think you could. It's a mindset. You could do it.

Really? Well, tell us about that. How did that feel?

Life-changing like to know that I could hike practically naked. The only thing is at the top like when I took my gloves off to take a video like then I started to really freeze. So I think the extremities need to be covered and I think you should have supervision if you're gonna try this. I want to try this by yourself but since I had warm gloves on I think I was able to do it but I remember how hiking the last 20 minutes, it was like a cliff coming off the side. The wind was whistling, you know, 50-60 miles an hour and can't see much and it's really cold. Like it was cold going up most of the mountain for the first three and a half hours, the last 30 minutes, it's just like there was no trees to protect you from the wind. It was a lot colder.

Are you shivering?

I was sweating still. I was sweating. So I had sweat coming down from the hat, cold, like, you know, you're generating heat and it just, it wasn't fun at the top. Like it started to hurt.

And you lose feeling in certain parts of your body?

Yeah, like my chest is like stinging and cold, but I think I got enough brown fat underneath me that I was like generating heat. I had a good layer of fat in my stomach, so I think that helped. But, you know, I went with a group of guys, so it was like this bonding experience. We're all in this together. I think if I did it alone, I probably would have stopped at one point where there was like a lodge at the top and then there was another 30 minutes. I think it would have stopped and be like, I did enough. Like, I proved it. I did three and a half hours. I got close to the top, but we were on a mission to reach the summit and doing it together. I think a positive mindset in general, maybe this isn't scientific, but I think having a positive attitude can get you through a lot of adversity. And what you speak out of your mouth can dictate the direction that you go in your life. And again, this probably isn't scientific or research, but if I say to myself as I'm getting to the top, I'm cold, I'm tired, I don't know if I can make it. This is stupid. What was I thinking? I'm probably going to convince my body to start getting colder and shutting down and looking backwards. But because we were like, man, it's sunny out. Like we were just saying, we're warm, it's hot, it's sunny. This is a great nice hike. Like we just kept speaking like these positive words. And we convinced ourselves, we believed it, our bodies started to believe it. Whatever we did, we were doing it together and we got to and I think what we say dictates a lot of our energy and our actions. So, I don't know if that's proven science or if that's just... Well, yeah.

You probably have to do that a few times to live longer, but yeah, but psychologically, it's changed your life?

Absolutely. I was trying to think, like it was a five-day trip, and I was.

Like.

Are there other weeks in my life that were better than this week. We, you know, going to the national championships to become an All-American was a big dream of mine and like every day leading up to it, but I was still in class. I was in school. It wasn't all fun. You know, playoffs in college football, like great weeks leading up to these games, right? But this was like every day we were taking on new challenges with a group of people. I don't know, something about it was really special. And Wim Hof is like this crazy character who's also helping a lot of people.

Yeah, he's great.

And he's getting people to get uncomfortable, which is going to help them fight disease, live longer, all these things that you talk about. Whether he knows the science 100% or not, he's doing things to get people to be uncomfortable on a consistent basis. And I think that helps people in general.

Right, physically and mentally.

Physically and mentally. We're doing breathing exercises every day. As you know, most people are very shallow breathers and that probably affects, I don't know, if you're shallow breathing your whole life, I don't think that can help you live longer, I'm assuming. I don't know the science. But just taking deep full breaths all the time and allowing the body to relax, it was so peaceful. I didn't look at my email once in a week. I didn't think about social media. I was just present, breathing, going through hard challenges. and it felt so peaceful and relaxing. I mean, it was discomfort and then like peace, discomfort and then like, ah.

Right.

Well, you need to experience adversity to be able to have the calm. Like we have in our lives. We know what suffering is. So that's why, you know, even on a bad day, it's still a pretty good day. Yeah. That's true. I get home and my wife, who's wonderful, she'll say, How was today? And after my mother died, I now say, even though it's a bit morbid, nobody died today. It was a great day. And that's my cutoff.

If someone dies, it's not the best day.

Right.

And if you've been through that, then all the other stuff is just minor.

Average. Average pain.

Yeah.

So the lesson here is push yourself. Do things that you don't think you're capable of doing. Experience adversity. It'll help you physically. even more so mentally.

-Yeah. How old do you think you can get to live? Like personally with all the research you've done now and with potentially in the next 20-30 years of science that you're going to discover, like if nothing happens physically with like a bus or something, how long do you think you personally can live if you optimized everything?

-Yeah.

-What'S possible? Not what's going to happen but what's possible.

-Right, right. Well, before I tell you that, I'm not doing this to live longer.

You don't want to live forever.

I wouldn't mind. I'm not looking forward to a horrible death. But that's not my goal here. It's not that I'm worried about myself. I do want to leave this planet having done something meaningful. That's what drives me mainly. But I'm also a scientist. I'm experimenting. I want to know stuff. Remember, you know, I told my friends we're the last generation. So I'm trying to accelerate knowledge at Harvard and at home. So I do these things to myself. I measure myself, glucose levels, whole bunch of parameters to see what's going on, not as proof but as indicators of what other people may test. And so I know from my own body that I'm still pretty young. I still need to do the definitive age test. We can now look at exactly how old we are.

Really? Like a ring of a tree.

It is. We've just. It's called the Horvath clock. It's the Pianist. You can measure how old the Pianist is within a few percent. So you can actually predict when you're gonna die. Really?

Have you. Have you predicted?

I gotta do it.

I gotta do it.

I've done a primitive form of that, which is in full disclosure. It's a company that. that I own a little bit of. But it. So this company takes blood tests. Can I say the name? Sure. It's called inside tracker. I mention it because people are gonna write to you about it. Sure. Sure. So inside tracker does blood test, and they measure a bunch of things, and i've been doing that for about 12 years. So I know i'm tracking myself and everything's staying young. Okay. And they can estimate your age. It's a rough estimate.

So you can estimate. your age by taking a blood sample.

Right, and measuring things in there that go up and down with it.

It's probably like a three-year swing either side or something or pretty close.

Yeah, it's an indicator of how well you're doing with your body. And I actually took a test a few years ago, many years ago, and I was, they came out as 58. I freaked out.

Because it made you older than what you are.

I was older than I was. I was 48 at the time. time.

Oh, what did you change?

Well, I upped some doses of molecules, took a couple more, and stopped eating badly. And the next test came out at 31. What?

Shut up. What do you mean stop eating badly? Like sugars and candies and cakes or is this like.

Well, I wasn't strictly intermittent fasting. I ate lunches. I had more fat than I do now. I'd eat pizza and things like that.

I love pizza.

Gosh. But I've turned it around. I've never been unhealthy. But this was a real-- that was a wake-up call. I have terrible genes. My father's side, we all died in our 70s, usually as males.

So what does it say that you can live to? You don't know yet.

Well, so I haven't answered your question. So that doesn't-- that says that I've probably got another 20 years extra, right?

Extra than the average lifespan.

Well, based on that blood test, we'll see.

Got it, got it.

But what could we live to? So here's the good news is that if we just continue on the trend that we've been on for 200 years, and it's been perfectly linear, so you can keep stretching it out. A child born today in the US can expect not hope but expect 50% of them to live to 104. So... And in Japan 107.

Oh my gosh.

If we keep going up... Now that's not going to happen by accident. That's going to take researchers like me to figure it out and a lot.

Of... And them doing the work and people actually not eating horrible and smoking and doing the things that help.

Hopefully that'll help too. That's why I wrote the book is to help people live longer.

It's just 100 years as lifespan now?

Well, yeah, that's the predicted trajectory. That's without any radical breakthrough. Wow. Without, you know, fixing the Pianist. Now, if we can fix the Pianist and truly reverse aging, like a reset switch, then who knows? And I.

We.

We could live 220. Maybe longer. It's hard to. Are you or. Well, yeah.

People born today.

You know, well. I'm going as fast as I can and we've got, we've had a big breakthrough in the last year that we found the reset switch, we think, in the cells to reset the age. So what's the next step?

It's like you guys are researching this for the next five, ten years, figuring out how to do that, reset it.

Well, we know how to do it in a mouse pretty easily.

That worked first time.

That was easy. Okay. And one of my students, another brilliant student, he decided to reverse the the age of the eye. So we took old mice that were basically blind and made their eyes young again so they could see just like they were young again.

Yeah.

So you could do that with people too?

Well, that's the next step. That's a few years away. But working, I'm an entrepreneur as you know, so I'm trying to push this out of the lab as fast as possible. But if it works on the eye, what else could it work on? Probably everything, I think. Now, is it safe? I think it is. We've given it to mice for a year and no problem. No cancer showing up or anything. Wow. But you don't want to push it too far. You don't want to go back to being an embryo. You'll be the world's biggest tumor.

Right. Right.

Wow. Wow. So what do you think you could live to personally?

Yeah.

You know, I'm trying to avoid the question because my peers, my colleagues. Sure, sure.

Hate it because it's.

It's unproven. It's unproven.

At you. But just like, you know, obviously it's not proven, but just. And if all goes well, and then, you know, we get sick and all these things don't happen. All right, so. So no traumatic events.

People are gonna rewind this video when I die, aren't they? So I'm on a trajectory to live well beyond 80 because I'm healthy.

Yeah.

My father's an example. He's 80. He's 80.

And you should live at least 10 years beyond that, right?

So at least that I should be healthy into my 90s. Be nice to break 100 with the Technologies and some of the medicines that I'm working on. And one of them that I'm actually taking maybe Beyond 100. That would be nice.

Wow.

In a healthy way. Playing tennis. Wow.

In a healthy way, Beyond 100.

A lot of people do that. Yeah, it's not for everybody, but. But you do see people in their hundreds that are still working and. happy.

How much does inflammation play into the longevity of your life?

Oh, it's huge. It's one of these hallmarks that if inflammation is going up too fast, that's basically your clock is ticking.

You're aging.

Accelerated, yeah.

So how do we get rid of inflammation?

Well, there are a number of ways. One is do these things and turn on your longevity genes, which are anti-inflammatory. Other ways I'm still taking a little aspirin every day. The data still looks pretty good for that.

Taking an aspirin.

Yeah, 81 milligrams a day.

That just takes away inflammation?

Yeah, mostly in your blood vessels. But you need to take it for a long time, of course, I think, to stop that. Resveratrol is anti-inflammatory. And remember how I said those mice have beautiful arteries, no fat on them?

Really?

So that's good. Yeah, but basically it's that. But overeating and being obese is gonna massively turn up inflammation. Within a few weeks, you'll do it. Just eating bad food for a few weeks will turn it up.

And fasting will kill inflammation.

Exactly. But you might say, well, if your immune system isn't overactive, what about getting sick? Turns out your immune system gets heightened, but inflammation Chronic inflammation gets dampened. So when you talk to a centenarian and say, Did you used to get sick? They say, I can't remember last time I got sick. Centenarian? Centenarian, people who live over 100. Okay. So that's a hormone. They don't remember when they got sick. They don't get sick. They rarely get even a sniffle or a cold.

How is that possible?

Well, they have massive immune systems. So even if someone sneezes on them, that virus is attacked and killed. But here's the thing, since I've been eating and living the right way over the last few years, since that terrible scary test, I haven't gotten sick.

No sickness. No cold, the flu.

No.

And I'm on planes, people are sneezing on me. We've got three kids, they're always sick.

What if you got like, what if you ate something that had like food poisoning that would fight against that too, or is that kind of hard to.

The question, I don't know. I don't know, but I haven't had chicken or something. I haven't had food poisoning recently, but it might just be that I can afford better food now.

That's good. I like that. Wow. This is all fascinating stuff. And I know you've got more in your book, Lifespan, why We Age and why We Don't have To. Make sure you guys get this book. Really powerful research and science. I got a couple questions left for you. This is called the Three Truths. I ask everyone at the end of my interviews. So I want you to imagine it's your last day on Earth and you're 150, 200 or however old you want to be. And you've done tons of research. You've written every book you want to write. You've answered every question that you can think of while you're alive. You publish all this information, but for whatever reason, you've got to take your work with you. So no one has access to your work anymore. more of your research. All your content is gone. It's going with you to another world.

-It sounds like hell, okay.

-Just imagine.

-Yeah.

But you get to leave behind three lessons or three things you know to be true from everything that you've learned in your life. You can write it down on a piece of paper. Everyone would have access to these three truths and this is the only three things you could share that they would have access to. What would you say are your three truths?

All right. Right, the first one that I live by is all about maximizing human potential. I believe that we're way underutilized. But for the individual, what you have to think every day is do something that's worth writing about or write something that's worth reading. So have an impact. That's my lesson, is don't settle for mediocrity. Do something spectacular and don't listen to the naysayers.

Mm-.

Okay.

Is that one?

That's one. The next one would be do something that scares you every day. Send off an email that you wouldn't be afraid to do. And along with that, when you're young, take risks like we did. You can fail, that's okay, you will fail, but it'll make you, it'll open you up to more opportunities. But also you'll be a stronger adult, stronger 40-50 year old.

Okay, that's two.

Ah gee, the third one, I haven't pre-prepared this, but this one's from the heart. I've described to you what it was like to see my mother pass away. And I spent my life arguing with my mother. I regret that. So as a parent now myself, let me tell the younger people, tell your parents how much you appreciate what they've done for you. Tell them that you love them, assuming that you do, if they're good people. because there will be a day, most likely, when they'll be gone and you won't have a chance to hug them anymore or see them anymore because they're gone. And when they're gone, you think, how is that possible that somebody can be there and not there within a matter of two minutes? That happens. And, yeah, I just wish that I'd told my mum more about how much I appreciated her. So I've dedicated the book to her because she cared more about herself than her kids.

Wow, special. Those are good three truths. I love those. I want to acknowledge you, David, for a moment for being obsessed about helping people. And I think your commitment and dedication to doing... I don't know what I've done for 10 years consistently, but doing research for 10 years on one thing and trying to get the most out of it and writing these books and taking the time to on my show and just being obsessed about helping people to leave a better, leave this world a better place. I think it's really admirable and I appreciate you. I acknowledge you for just showing up every single day and doing the work. Even when your peers criticize you and even when the media does this, like I know how not easy that is when you're shamed publicly. It's not easy to keep going. But I acknowledge you for pushing through any insecurities or emotional traumas that you faced to try to help people like me and everyone watching to live better. So, thank you for all that you do. And I want to make sure people get the book. Lifespan, where can we connect with you online?

Well, I have a website called lifespanbook.com. I have a newsletter. So, that's keeping things up to date. New stuff I write about every few weeks. And I'm on social media, Instagram and Twitter, Facebook.

-Where do you hang out the most personally? What's your social media?

Instagram and Twitter.

Okay, cool. What's your Instagram?

It's David Sinclair PhD.

Okay, cool. So we'll connect with you there. Make sure you guys send him some messages over on Instagram. This is my final question. It's what's your definition of greatness?

Again, off the cuff. So I would say, I would have, If you asked me a few years ago, I probably would have said something a little bit self-centered, which is, Greatness is somebody who is recognized internationally for something important. But I don't think that anymore. I'm married to a woman who has a PhD from MIT in genetics, who could have been a superstar scientist, but instead chose to do non-profit work and raise a family and put up with me. That's greatness. So you don't have to be internationally recognized. You just need to make a difference in people's lives.

Wow. I love it. Thanks, man. Appreciate this.

Thanks, Louis. Thanks for what you do, too.